Analysis of the genomes of replication competent oncoviruses demonstrated that a major progenitor of the pol genes of these viruses gave rise to mammalian type C viruses and another gave rise to types A, B, D, and avian type C oncoviruses. Unusual patterns of homology among the env genes of mammalian type C and D onco-viruses revealed the occurrence of genetic interactions between their progenitors and suggests that such interaction contributed to their evolution. Studies on human proto-oncogenes provided information on the chromosomal localization of members of the ras gene family and the myb proto-oncogene. The ras genes were found to be widely dispersed in the human genome (H-ras-1, chromosome 11; K-ras-1 chromosome 6; K-ras-2, chromosome 11; N-ras, chromosome 1). C-myb was localized to chromosome 6. These findings are being pursued in regard to the specific chromosomal rearrangements that are known to occur in certain human tumors. Structural analysis of the c-sis (human) proto-oncogene showed that a 45-kbp region of human DNA contains all the coding regions of the v-sis oncogene. These sequences are present as six exons, five of which contain the open reading for the sis gene product, p28. An additional 5' coding sequence was identified. Sequence analysis demonstrated that the c-sis gene codes for platelet-derived growth factor chain 2. It was possible to demonstrate that the c-sis (human) proto-oncogene possesses transforming potential.